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Pharmacokinetic–pharmacodynamic integration of orbifloxacin in Japanese quail ( Coturnix japonica ) following oral and intravenous administration

2010; Wiley; Volume: 34; Issue: 4 Linguagem: Inglês

10.1111/j.1365-2885.2010.01233.x

1365-2885

Michelle G. Hawkins, Ian Taylor, Barbara A. Byrne, Ray Armstrong, Lisa A. Tell,

Pneumonia and Respiratory Infections

Hawkins, M. G., Taylor, I. T., Byrne, B. A., Armstrong, R. D., Tell, L. A. Pharmacokinetic–pharmacodynamic integration of orbifloxacin in Japanese quail ( Coturnix japonica ) following oral and intravenous administration. J. vet. Pharmacol. Therap. 34 , 350–358. The pharmacokinetics of single‐dose administration of orbifloxacin were determined in Japanese quail ( Coturnix japonica ) at dosages of 5 mg/kg intravenous (i.v. n = 12) and 7.5 mg/kg oral (p.o.; n = 5), 10 mg/kg p.o. ( n = 5), 15 mg/kg p.o. ( n = 12) and 20 mg/kg p.o. ( n = 5) via HPLC. Orbifloxacin minimal inhibitory concentrations (MICs) against 22 microbial isolates from various bird species were performed to calculate pharmacodynamic surrogate markers. The concentration–time data were analyzed using a naïve pooled data (NPD) approach and compartmental and noncompartmental methods. Steady‐state volume of distribution (Vd ss ) and total body clearance (Cl) after i.v. administration were estimated to be 1.27 L/kg and 0.60 L/h·kg, respectively. Following 15 and 20 mg/kg p.o. dose, bioavailability was 102% and 117%, respectively. The harmonic mean of the corresponding terminal half‐lives (T 1/2 λ z ) across all the dose groups was 1.71 h. The C max /MIC 90 and AUC 0∞24 /MIC 90 for the 15 and 20 mg/kg p.o. doses were ≥5.22 and ≥8.98, and ≥25.80 and ≥39.37 h, respectively. The results of this study suggest that 20 mg/kg orbifloxacin p.o. would be a rational daily dose to treat susceptible infections in Japanese quail not intended for food consumption. For more sensitive bacterial organisms, 15 mg/kg p.o. may also be effective.